The present invention is a novel compound which is a 3,5-di-t-butyl-4-hydroxyphenylmethylhydroxylamine or derivative thereof and a pharmaceutically acceptable acid addition or base salt thereof, pharmaceutical composition and methods of use therefor. The invention compounds are now found to have activity as inhibitors of one or both of cyclooxygenase and 5-lipoxygenase providing treatment of conditions advantageously affected by such inhibition including inflammation, arthritis, pain, fever, and the like. Thus, the present invention is also a pharmaceutical composition or method of use thereof.
The following are references disclosing related derivatives.
U.S. Pat. No. 4,673,692 or EP Application 0185158 discloses diphenylmethylimine derivatives where one of the phenyls is a 3,5-di-t-butyl-4hydroxyphenylmethyl moiety useful for the treatment of inflammation, pain, or rheumatism.
JO 3109263 described in Derwent Abstract No. 91-181443/25 discloses 2,6-di-t-butyl-4[amino(phenyl)methylene]-2,5-cyclohexadien-1-ones and derivatives including substitutions on both the amino and phenyl groups for use as inhibitors of arachidonic acid, cyclooxygenase and lipoxygenase inhibitors.
JO 3052849 discloses oxime intermediates providing 3,5-di-t-butyl-4-hydroxy-diphenylmethyl amine derivatives as antiinflammatory agents, antirheumatics, and analgesic agents (see Derwent Abstract No. 91-112647/16.
U.S. 5,066,679 discloses di-t-butyl substituted phenolic thioalkylamides as inhibitors of 5-lipoxygenase.
These disclosures differ structurally from the present invention by the absence of the combination of a 3,5-di-t-butyl-4-hydroxyphenyl and a selected optionally substituted phenyl, thienyl, furanyl, isoxazolyl, or heterocyclic group through a methylene bridge where the methylene is further substituted by a substituted hydroxylamine.